The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked release of [3H]D-aspartate
([3H]D-ASP) from mouse cortical synaptosomes were investigated. The mGlu1/5 receptor agonist
3,5-DHPG (0.1–100 mM) potentiated the Kþ(12 mM)-evoked [3H]D-ASP overflow. The potentiation occurred
in a concentration-dependent manner showing a biphasic pattern. The agonist potentiated [3H]DASP
exocytosis when applied at 0.3 mM; the efficacy of 3,5-DHPG then rapidly declined and reappeared at
30–100 mM. The fall of efficacy of agonist at intermediate concentration may be consistent with 3,5-DHPGinduced
receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by 0.3 mM 3,5-DHPG was
prevented by the selective mGlu5 receptor antagonist MPEP, but was insensitive to the selective mGlu1
receptor antagonist CPCCOEt. In contrast, CPCCOEt prevented the potentiation by 50 mM 3,5-DHPG, while
MPEP had minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced effects.
A total of 0.3 mM 3,5-DHPG failed to facilitate the Kþ-evoked [3H]D-ASP overflow from mGlu5 receptor
knockout (mGlu5/) cortical synaptosomes, but not from nerve terminals prepared from the cortex of
animals lacking the mGlu1 receptors, the crv4/crv4 mice. On the contrary, 50 mM 3,5-DHPG failed to
affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from crv4/crv4 and mGlu5/mice.
Western blot analyses in subsynaptic fractions support the existence of both mGlu1 and mGlu5 autoreceptors
located presynaptically, while immunocytochemistry revealed their presence at glutamatergic
terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on mouse glutamatergic cortical
terminals; mGlu5 receptors may represent the ‘‘high affinity’’ binding sites for 3,5-DHPG, while mGlu1
autoreceptors represent the ‘‘low affinity’’ binding sites.

The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked release of [3H]D-aspartate
([3H]D-ASP) from mouse cortical synaptosomes were investigated. The mGlu1/5 receptor agonist
3,5-DHPG (0.1–100 mM) potentiated the Kþ(12 mM)-evoked [3H]D-ASP overflow. The potentiation occurred
in a concentration-dependent manner showing a biphasic pattern. The agonist potentiated [3H]DASP
exocytosis when applied at 0.3 mM; the efficacy of 3,5-DHPG then rapidly declined and reappeared at
30–100 mM. The fall of efficacy of agonist at intermediate concentration may be consistent with 3,5-DHPGinduced
receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by 0.3 mM 3,5-DHPG was
prevented by the selective mGlu5 receptor antagonist MPEP, but was insensitive to the selective mGlu1
receptor antagonist CPCCOEt. In contrast, CPCCOEt prevented the potentiation by 50 mM 3,5-DHPG, while
MPEP had minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced effects.
A total of 0.3 mM 3,5-DHPG failed to facilitate the Kþ-evoked [3H]D-ASP overflow from mGlu5 receptor
knockout (mGlu5/) cortical synaptosomes, but not from nerve terminals prepared from the cortex of
animals lacking the mGlu1 receptors, the crv4/crv4 mice. On the contrary, 50 mM 3,5-DHPG failed to
affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from crv4/crv4 and mGlu5/mice.
Western blot analyses in subsynaptic fractions support the existence of both mGlu1 and mGlu5 autoreceptors
located presynaptically, while immunocytochemistry revealed their presence at glutamatergic
terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on mouse glutamatergic cortical
terminals; mGlu5 receptors may represent the ‘‘high affinity’’ binding sites for 3,5-DHPG, while mGlu1
autoreceptors represent the ‘‘low affinity’’ binding sites.